P1, N=398, Recruiting, Astellas Pharma Global Development, Inc. | Trial completion date: May 2027 --> May 2028 | Trial primary completion date: Nov 2026 --> May 2028

The approved antibody zolbetuximab requires higher expression levels (≥75% of tumor cells with 2-3+ membranous staining), yet broader thresholds are increasingly explored...Broadening the threshold for positivity identified nearly three-quarters of patients as CLDN18.2 positive, underscoring the impact of selection cut points on trial eligibility. These findings highlight the potential to expand patient access to CLDN18.2-targeted therapies using lower thresholds.

Specimen type (biopsy or surgical resection) had no apparent impact on treatment outcomes. Within the approved CLDN18-positive threshold, the semiquantitative staining proportion showed no detectable differences in the efficacy or safety of zolbetuximab plus chemotherapy.

Anti-CLDN18.2 therapy, primarily consisting of first-line zolbetuximab combined with chemotherapy, significantly improved progression-free survival (PFS) (hazard ratios [HR] 0.564; 95% confidence interval [CI]: 0.417-0.711) and overall survival (OS) (HR 0.716; 95% CI: 0.631-0.802), along with enhanced 1- and 2-year survival rates...Standardized definitions for CLDN18.2 positivity and high expression are urgently needed. www.crd.york.ac.uk/prospero identifier is CRD420251123719.

P1, N=13, Terminated, Zhejiang Doer Biologics Co., Ltd. | N=94 --> 13 | Trial completion date: Jun 2025 --> Mar 2026 | Recruiting --> Terminated | Trial primary completion date: Jun 2025 --> Dec 2025; This trial was terminated voluntarily by the Sponsor for reasons related to its corporate strategic development, with no safety concerns or efficacy signals related to the investigational product identified.

In this study, we demonstrated that IBI389 effectively redirects T cells to CLDN18.2-expressing tumors, suppresses tumor growth, and synergizes with PD-1 blockade and has a favorable safety profile. By virtue of its ability to enhance immune infiltration, remodel cytokine responses, and reduce tumor-immune spatial separation, IBI389 may have considerable potential as a novel therapeutic strategy for CLDN18.2-positive gastric cancer and related malignancies.

Identifying practice barriers and proactively addressing them can result in a more rapid adoption of new therapies. This study identified 4 major challenges to the adoption of the novel targeted agent, zolbetuximab, in the community practice setting: limited awareness of clinical trial data, inadequate biomarker testing infrastructure, uncertainty in identifying optimal patient populations, and access barriers related to cost and insurance coverage. By implementing strategies identified from this study, we hope to accelerate and improve future adoption to innovative treatments in the community oncology setting, ultimately improving patient outcomes.

Real-world implementation of zolbetuximab is complicated by cumbersome administration times, short drug stability, extended observation time, and difficult tolerability. This report describes our experience in implementing zolbetuximab in clinical practice and provides an extensive drug evaluation.

P1, N=330, Recruiting, I-Mab Biopharma US Limited | N=168 --> 330 | Trial completion date: Dec 2026 --> Dec 2027 | Trial primary completion date: Dec 2025 --> Dec 2026